OP0175 TYPE OF mRNA COVID-19 VACCINE AND TREATMENT INFLUENCE ANTIBODY KINETICS IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES
Authors: C. E. Raptis, D. O. Andrey, C. Polysopoulos, C. Berger, A. Ciurea, P. Lescuyer, T. Maletic, M. Riek, A. Scherer, I. von Loga, J. Safford, K. Lauper, B. Moeller, N. Vuilleumier, A. Finckh, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients on immunomodulatory treatments mount an attenuated immune response following mRNA COVID-19 vaccination, yet long-term studies of vaccine-induced anti-SARS-CoV-2 antibody (Ab) kinetics are missing. Objectives In this prospective observational study, we mapped the humoral antibody response to mRNA COVID-19 vaccines up to 24 weeks post full vaccination in patients with inflammatory rheumatic diseases (IRDs). We aimed to assess differences due to treatment, age, past SARS-CoV-2 infection, and vaccine (BNT162b2 vs. mRNA-1273). Methods Adult patients from the SCQM cohort who assented to an mRNA COVID-19 vaccine were recruited between 3/21 – 9/21. Participants answered questionnaires via an app and received kits for the self-collection of capillary blood samples at baseline, 4, 12, and 24 weeks post full vaccination. Samples were tested for IgG Ab against the S1 domain of the SARS-CoV-2 spike protein (anti-S1-IgG) using the EUROIMMUN ELISA. To examine differences in Ab titres arising from the defined parameters, while accounting for inter-assay variability, mixed effects continuous outcome logistic regression models were applied at each timepoint. Results Samples were obtained from 570 patients: 67% female, mean age 53 y (SD 12 y) with 37% RA, 36% axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARDs &amp; no glucocorticoids; 15%), csDMARDs (10%), TNFi (48%), IL-1/6/17/23i (14%), JAKi (6%), rituximab (RTX; 4%), or abatacept (ABA; 2%) in mono/combination therapy at the first vaccination. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. For any Ab threshold, the odds of having a higher Ab titre at 4, 12, and 24 weeks post full vaccination were 3.3 – 4 times higher with mRNA-1273 compared to BNT162b2 (Table 1, Figure 1). TNFi, JAKi, RTX, and ABA as monotherapy resulted in significantly lower Ab levels compared to no medication at almost all timepoints. In combination therapy, TNFi, IL-1/6/17/23i, RTX, and csDMARDs led to consistently lower Ab titres at all timepoints compared to respective monotherapy. Table 1. The OR of being above a given Ab threshold, regardless of the threshold. Ref. levels: mean age, no medication, no past SARS-CoV-2 inf., BNT162b2. Included in model but not shown: diagnosis, infrequently used medication (all non-signif.) Weeks post full vacc. 4 12 24 OR (95% CI); p Age 0.96 (0.94 – 0.97) **** 0.98 (0.96 – 0.996) * 0.98 (0.97 – 1.00) mRNA-1273 (vs BNT162b2) 3.28 (2.34 – 4.61) **** 3.96 (2.83 – 5.54) **** 3.94 (2.93 – 5.50) **** Past COVID inf. (vs none) 7.56 (4.32 – 13.2) **** 8.14 (4.78 – 13.86) **** 11.65 (6.62 – 20.50) **** csDMARD † 1.27 (0.67 – 2.41) 1.78 (0.94 – 3.35) 1.70 (0.86 – 3.36) TNFi † 0.46 (0.28 – 0.71) **** 0.30 (0.19 – 0.48) **** 0.13 (0.081 – 0.22) **** IL-1/6/17/23i † 0.97 (0.54 – 1.75) 1.04 (0.57 – 1.89) 0.89 (0.49 – 1.64) JAKi † 0.38 (0.16 – 0.91) * 0.38 (0.16 – 0.91) * 0.53 (0.22 – 1.28) RTX † 0.078 (0.013 – 0.46) ** 0.078 (0.015 – 0.42) ** 0.16 (0.037 – 0.71) * ABA † 0.14 (0.039 – 0.51) ** 0.087 (0.022 – 0.35) *** 0.068 (0.017 – 0.27) *** Interactions § Age:vaccine ‡ 1.04 (1.02 – 1.07) ** 1.02 (0.99 – 1.05) 1.03 (1.0008 – 1.058) * csDMARD:combi 0.12 (0.02 – 0.70) * 0.17 (0.029 – 0.95) * 0.11 (0.023 – 0.56) ** TNFi:combi 0.34 (0.20 – 0.59) *** 0.37 (0.22 – 0.61) *** 0.36 (0.21 – 0.62) *** IL-1/6/17/23i:combi 0.26 (0.09 – 0.78) * 0.25 (0.085 – 0.70) ** 0.20 (0.071 – 0.58) ** JAKi:combi 1.76 (0.33 – 9.44) 1.23 (0.32 – 4.70) 0.95 (0.25 – 3.65) RTX:combi 0.11 (0.01 – 0.87) * 0.095 (0.012 – 0.73) * 0.085 (0.0091 – 0.79) * ABA:combi 1.75 (0.25 – 12.2) 0.74 (0.096 – 5.75) 0.51 (0.073 – 3.62) * p &lt; 0.05; ** p &lt; 0.01; *** p &lt; 0.001; **** p &lt; 0.0001; † Medication as monoth. vs no medication ‡ Interaction terms showing how OR of mRNA-1273 (vs BNT162b2) increases with age § Interaction terms with medications: medication in combination th. vs medication as monoth. Conclusion Compared to no medication, some immunomodulatory therapies resulted in markedly lower Ab levels at all timepoints. In IRD patients, a past SARS-CoV-2 infection resulted in strikingly increased immunogenicity, as did mRNA-1273 compared to BNT162b2. Acknowledgements This study is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM thanks the patients for their participation in this study. A list of rheumatology offices and hospitals that contribute to the SCQM registries can be found on www.scqm.ch/institutions . The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors . Disclosure of Interests Catherine Elizabeth Raptis Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Diego Olivier Andrey: None declared, Christos Polysopoulos Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Christoph Berger: None declared, Adrian Ciurea: None declared, Pierre Lescuyer: None declared, Tanja Maletic Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Myriam Riek Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Almut Scherer Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Isabell von Loga Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Judith Safford: None declared, Kim Lauper Speakers bureau: Kim Lauper reports consulting fees for Pfizer and speakers fees for Pfizer, Viatris and Celltrion outside of the submitted work., Consultant of: Kim Lauper reports consulting fees for Pfizer and speakers fees for Pfizer, Viatris and Celltrion outside of the submitted work., Burkhard Moeller: None declared, Nicolas Vuilleumier: None declared, Axel Finckh Speakers bureau: Axel Finckh has received consultancies or speaker honoraria for AbbVie, BMS, Eli-Lilly, Gilead, Pfizer, Sanofi, and UCB outside of the submitted work, Consultant of: Axel Finckh has received consultancies or speaker honoraria for AbbVie, BMS, Eli-Lilly, Gilead, Pfizer, Sanofi, and UCB outside of the submitted work, Grant/research support from: Axel Finckh has received research support from AbbVie, Eli-Lilly, Galapagos, and Pfizer outside of the submitted work, Andrea Rubbert-Roth: None declared